Until recently, Kaposi's sarcoma was considered a rare neoplasm in the United States. In the past two years, a strikingly increased incidence was observed, primarily in young homosexual males with acquired immunodeficiency syndromes (AIDS) and to a lesser degree in renal transplant recipients. A feature common to both these situations is the frequency of active cytomegalovirus (CMV) infection. Epidemiologic studies suggest an association between CMV and Kaposi's sarcoma in other populations as well. Two ways in which CMV may predispose to Kaposi's sarcoma are by direct transformation of appropriate target cells or by indirect suppressive effects on immunoregulatory control mechanisms. We will explore both of these possibilities by studying high risk subjects for CMV infections and immunological defects, and by attempting in vitro transformation of potential target cells with CMV isolates from such individuals. In addition, we will study the possible interaction of CMV and chemicals such as nitrites in target cell transformation. Although CMV has been the virus most closely associated with AIDS and Kaposi's sarcoma, other viruses may also be involved in these syndromes. Epstein-Barr virus (EBV) and the newly described human T cell leukemia virus (HTLV) are possible offenders. We will evaluate high risk patients sequentially for infection with these agents and attempt to assess their importance in the pathogenesis of subsequent syndromes.